MeCP2 knockdown reveals DNA methylation-independent gene repression of target genes in living cells and a bias in the cellular location of target gene products

• Yakabe Shinya

  Division of Molecular Genetics and Epigenetics, Department of Biomolecular Sciences, Faculty of Medicine, Saga University Division of General Surgery, Department of Surgery, Faculty of Medicine, Saga University

• Soejima Hidenobu

  Division of Molecular Genetics and Epigenetics, Department of Biomolecular Sciences, Faculty of Medicine, Saga University

• Yatsuki Hitomi

  Division of Molecular Genetics and Epigenetics, Department of Biomolecular Sciences, Faculty of Medicine, Saga University

• Tominaga Hirotaka

  Section of Clinical Cooperation System, Center for Comprehensive Community Medicine, Faculty of Medicine, Saga University

• Zhao Wei

  Department of Cardiovascular Medicine, Shanghai Shuguang Hospital Affiliated with Shanghai University of T.C.M.

• Higashimoto Ken

  Division of Molecular Genetics and Epigenetics, Department of Biomolecular Sciences, Faculty of Medicine, Saga University

• Joh Keiichiro

  Division of Molecular Genetics and Epigenetics, Department of Biomolecular Sciences, Faculty of Medicine, Saga University

• Kudo Shinichi

  Hokkaido Institute of Public Health

• Miyazaki Kohji

  Division of General Surgery, Department of Surgery, Faculty of Medicine, Saga University

• Mukai Tsunehiro

  Saga University

抄録

MeCP2, a methyl-CpG binding domain (MBD) protein, is known to bind to methylated CpG sites via a conserved MBD, leading to transcriptional repression. However, studies in cell-free system for gene repression and MeCP2 binding have suggested that DNA methylation-independent repression also occurs in living cells. It has been difficult to characterize the target genes of MeCP2 because a limited number have been identified to date. In this context, we screened for MeCP2 target genes using knockdown (KD) experiments combined with microarray gene expression analyses. Of the 49 genes that showed a more than three-fold increase in expression in two independent KD experiments conducted with different siRNA sets, unexpectedly, half (24 genes) did not contain promoter CpG islands (CGIs). Of seven selected genes that did contain CGIs, only two were methylated at the CGI, bound MeCP2 before KD, and reduced MeCP2 after KD. For three, MeCP2 was observed to bind to the unmethylated CGI before KD, and for one MeCP2 was reduced after KD. Another two genes neither had DNA methylation nor bound MeCP2 before KD. Gene ontology analysis suggested that MeCP2 represses a certain group of genes. These results suggest that in addition to the canonical gene repression function, MeCP2 can repress gene expression by binding to unmethylated DNA in particular genes in living cells.<br>

収録刊行物

• Genes & Genetic Systems

  Genes & Genetic Systems 83 (2), 199-208, 2008

  日本遺伝学会

キーワード

• CpG island
• DNA methylation
• gene ontology
• gene repression
• MeCP2

詳細情報

• CRID: 1390001205472592384
• NII論文ID: 10024396087
• NII書誌ID: AA11077421
• DOI: 10.1266/ggs.83.199
• ISSN: 18805779
• ISSN: 13417568
• NDL書誌ID: 9476533
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I9476533
• Web Site: http://www.jstage.jst.go.jp/article/ggs/83/2/83_2_199/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2008279585
• 本文言語コード: en
• データソース種別:
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